Reinscheid Rainer K, Civelli Olivier
Institute of Pharmacology and Toxicology, University Hospital Jena, Friedrich-Schiller-Universität, Jena, Germany.
Institute of Physiology I, University Hospital Münster, Westfälische-Wilhelms-Universität, Münster, Germany.
Handb Exp Pharmacol. 2019;254:3-16. doi: 10.1007/164_2018_195.
The discovery of nociceptin/orphanin FQ (N/OFQ) marks the genuine start of the reverse pharmacology era, when systematic hunting for ligands of orphan receptors began. The choice of this particular target was no coincidence as the orphan receptor ORL-1 displayed high similarity to known opioid receptors, and thus its elusive ligand held promise to find more than a ligand but a missing opioid peptide. N/OFQ indeed turned out to belong to the opioid peptide family, but with significant pharmacological and functional distinctions. The quest for understanding N/OFQ's physiological functions has produced some novel insights into stress regulation and many other body functions but is still ongoing almost 25 years after its discovery. This chapter highlights the early steps of orphan receptor research and some of the protagonists who helped to advance the field.
孤啡肽/痛敏肽（N/OFQ）的发现标志着反向药理学时代的真正开端，彼时对孤儿受体配体的系统性搜寻拉开帷幕。选择这个特定靶点并非偶然，因为孤儿受体ORL-1与已知的阿片受体高度相似，因此其难以捉摸的配体有望找到的不仅仅是一种配体，而是一种缺失的阿片肽。N/OFQ后来确实被证明属于阿片肽家族，但在药理学和功能上有显著差异。对N/OFQ生理功能的探索为应激调节和许多其他身体功能带来了一些新见解，但在其发现近25年后，这一探索仍在继续。本章重点介绍孤儿受体研究的早期阶段以及一些推动该领域发展的关键人物。
